1. Field of the Invention
The present invention relates to polypeptides and to their preparation. The polypeptides have been isolated from the leech Hirudinaria manillensis. The polypeptides have anti-thrombin properties.
2. Discussion of the Background
The most popular anticoagulant peptides are probably those belonging to the family of himdins. Hirudin, originally isolated from the medicinal leech, Hirudo medicinalis, is a well known and well characterized polypeptidic inhibitor of thrombin.sup.1,2. More particularly, it binds thrombin by ionic interactions thus preventing the cleavage of fibrinogen to fibrin and the subsequent fibrinclot formation. In animal studies hirudin has demonstrated efficacy in preventing venous thrombosis, vascular shunt occlusion and thrombin-induced disseminated intravascular coagulation. In addition, himdin exhibits low toxicity, little or no antigenicity and a very short clearance time from circulation..sup.3
Polypeptides with anticoagulant properties have been isolated from a different leech species, Hirudinaria manillensis (EP-A-0347376 and WO 90/05143). This leech evolutionarily more advanced than Hirudo medicinalis and could therefore synthesize anticoagulant peptides whose amino acid sequences may be different from those of hirudin and other known hirudin variants.
We have analysed a preparation obtained from Hirudinaria manillensis leeches. We have found three new polypeptides having anti-thrombin activity. Accordingly, the present invention provides a polypeptide comprising the amino acid sequence: ##STR1## and pharmaceutically acceptable salts thereof.